Monoclonal antibodies against human anti-F(ab')2 antibodies react with light chain epitopes

Anti-F(ab′)2 antibodies affinity isolated from sera of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or normal SLE relatives were used to produce monoclonal antibodies (mAbs) in Balb c and NZB mice. Four of five mAbs showed only primary light chain specificity. Only one mAb produced in an NZB mouse against anti-F(ab′)2 from a single SLE patient showed anti-μ-chain specificity. Parallel identical control immunizations with IgG or a single human IgG κ myeloma produced mAbs with a predominant γ-chain Fc fragment specificity. Anti-light chain specificity of mAbs was demonstrated to involve epitopes requiring tertiary structure of the entire light chain instead of antigens confined to C κ λ or V κ λ fragments. Anti-κ specificity of three mAbs was extremely similar but not identical to that defined by anti-Kml allotyping systems. No evidence was obtained with any of the mAbs produced for antigens unique to SLE or RA anti-F(ab′)2 antibodies. The light chain antigenic prominence of many anti-F(ab′)2 antibodies may reflect structural features shared by this group of immunoglobulins some-how important for their biologic function.